Values Statement

The overall aim of this study is to investigate the role of impulsivity as an endophenotype for drug addiction.

Although impulsivity is considered one of the strongest candidate endophenotypes for addiction, progress in the field is hampered by: (1) the heterogeneity of impulsivity, characterized by multiple personality, psychiatric, and neurocognitive dimensions; (2) the heterogeneity of addiction phenotypes, in part related to the high rates of polysubstance dependence among drug users; and (3) the lack of objective quantitative methods for optimal endophenotype selection and the limited number of studies addressing the full endophenotype criteria. To address these challenges, we have developed a program of addiction research in Bulgaria, a key transit country for heroin trafficking and a major European center for production of synthetic amphetamine-type stimulants. This has allowed us to access rare populations of predominantly monosubstance-dependent heroin and amphetamine users, many in protracted abstinence. Our preliminary results reveal a complex relationship between personality/psychiatric (trait) and neurocognitive (state) dimensions of impulsivity, often manifested in opposite directions in heroin and amphetamine dependent individuals. Pilot computational modeling analyses of decision-making, a central neurocognitive aspect of impulsivity has proved particularly informative by indicating that different mechanisms may underlie the impaired decision-making of opiate and stimulant users. Our findings underscore the utility of examining multiple and more narrowly-defined dimensions of impulsivity and contribute significantly to a growing body of literature that reveals important differences between chronic users of different classes of drugs.